Where
possible try to use "bio-identical" hormones. These are
the ones that are molecularly identical to those which are produced
naturally by the human body. Synthetic hormones
are purposely designed to be more difficult for the body to metabolize
and break down so they will remain active for longer periods in the
bloodstream. There are additional problems with these drugs as they
can place undue stress on the liver and cause the build up of "molecular
junk" made up of left-over bits the body cannot metabolize. For
example the popular HRT drug Premarin (conjugated estrogen) is derived
from pregnant mare urine - hence the name "Premarin." The
estrogen are HORSE estrogens, not HUMAN estrogens. There are elements
to the molocule that are normally metabolized by enzymes in a horse's
body that simply do not exist in a human being. Where possible use
REAL "17-beta Estradiol" and "Micronized Progestrone."

GO
TRANSDERMAL

Administration
is another important consideration. Most of the synthetic estrogens
are an oral administration, which must first pass through the liver
before entering the blood stream. This is the complete reverse of
the way the body processes estrogen it makes itself, which travels
through the blood stream and only the left-over hormone passes into
the liver where it is broken down and cleaned from the body. Oral
estrogens are given in high doses because they must be able to "overwhelm"
the liver's ability to break them down. A portion of them will make
it through the liver into the blood stream, but what doesn't puts
stress on the liver and produces byproducts which are known to be
"liver toxic" thus damaging the liver. The most effective
means of absorbtion is via injection. However there is the added risk
of infection and large doses must be given that wear off over time,
causing a "roller coaster" of peaks and valleys in hormone
levels. There is no advantage to recreating a woman's cycle if one
doesn't have ovaries or a uterus! The second most effective means
of delivery is "transdermal." For 17-beta Estradiol there
are a number of transdermal patches (Climera, Vivelle, Estraderm)
on the market that fit the bill. They provide a steady dose over time
of bio-identical estrogen. The FDA recently approved an Estradiol
Lotion (Estrasorb) that may be a promising alternative to the patches.
A similar product, an Estradiol Gel called "Sandrena" has
been available in Europe for a while. Some oral estrogens may be slowly
dissolved under the tongue for sublingual usage, though this is not
the intended nor recommended method by the manufacturers and data
relating to the effectivenes is largely anecdotal. A final option
is to take estradiol nasally. There is one estrogen nasal spray on
the market (Aerodiol) for which the manufacturer claims good absorbtion
through the mucous membranes in the sinuses.

NOTE:
The aforementioned methods of administration work fine for smaller
doses (i.e., "beginner" doses to see how well you tolerate
the medication or maintenance doses post-operatively). For higher
dosing these methods of delivery can be cumbersome. For example, to
get the equivelent of 6mg Oral Estradiol from a patch you'd have to
wear four Climera 100 Patches concurrently. Since you aren't supposed
to place a patch on the same spot two weeks in a row, and you're only
supposed to put them on your buttocks or abdomen, most people would
quickly run out of locations on their body to place the patches. Nasal
sprays and gels could be applied several times over the course of
a day, but most people find intramuscular injections or dissolving
oral estradiol pills under their tongues (or between the cheek and
gum) preferable alternatives when a higher actively "feminizing"
dose is desired. Lower doses tend not to cause much feminization and
transdermal patches in particular are often reported to be inadequate
for that purpose. Nonetheless many doctors like to start people out
on the patch because there are very low incidence of side effects
reported from them and it is nearly impossible for patients to overdose
on them (doctors are well aware that TS patients are often IMpatient
to be feminized and tend to "mega-dose" on orals, which
is not only dangerous but also costly and wasteful).

For
progesterone there are lotions and "breast creams" which
are infused with Micronized Progesterone. Some of these are available
without a prescription from compounding pharmacies. Even if they are
"prescription strength" the dosage levels can be inconsistent
if the progestrone is not thoroughly mixed with the cream and the
amount used exactly the same each time. Another option may be Prometrium,
which is an oral administration that has micronized progesterone in
a gel cap suspension of peanut oil.

BLOCK
ANDROGENS

Aldactone/Spironolactone:
The preferred general anti-androgen is Spironolactone (Aldactone).
This drug is primarily used as an anti-hypertensive and shouldn't
be used by people with low blood pressure. Another side-effect is
that it increases the amount of intracellular potassium, which can
lead to the potentially life threatening problem called Hyperkalemia.
This can usually be managed with diet and regular blood monitoring.
It is also a diuretic so remaining properly hydrated is also crucial
to maintaining good health. Okay, so what does it DO? A couple of
things: first and foremost it competes with Dihydrotestosterone (DHT)
at hormone receptor points. DHT is believed to be the cause of non-genetic
male-pattern baldness and excess facial/body hair. The other thing
Spironolactone does is block the expression of the P-450 gene1
that, among other things, stimulates progesterone to testosterone
conversion [ see the section titled "Hormone
Chain Explained" ]. I have also found information claiming
that the topical form of Spironolcatone (available as a foam) is the
preferable method of delivery for blocking DHT at the skin - if the
primary purpose of using the drug is to hamper body/facial hair growth
and/or male pattern balding.

A
word of caution. I've heard of people trying to take Spironolactione
sublingually by dissolving it under their tongue. First of all the
pills taste absolutely terrible so that should be enough incentive
not to try dissolving them in your mouth. The other thing is that
the few people who've tried it have reported bleeding gums and sores
afterwards. It is not intended to be taken this way and you would
seriously risk overdosing by doing so, which could lead to a heart
attack.

Finasteride:
Probably better known by the brand name versions, Propecia and Proscar.
This drug is popular as a treatment for male-pattern baldness. Like
Spironolactione it targets DHT hormones, however it doesn't block
DHT receptor points as Spironolactone does. Instead it does what Natural
Progesterone does - blocks the activity of the 5-alpha-reductase enzyme
in an effort to prevent the conversion of testosterone into DHT. For
patients seeking to reverse a receding hairline, they often use Minoxidil
(Rogaine) as well. This may be undesirable to M2F TS patients, however,
because Minoxidil can often have a systemic effect (i.e., it causes
hair growth elsewhere on the body, not just where it was applied).
For most M2F patients the object of DHT reduction is to slow/reduce
unwanted facial and body hair. If that is the objective, Spironolactone
has been shown in studies on women with Hirsutism to be more efffective
at reducing unwanted hair than Finasteride[ source
]. Finasteride used in conjunction with Spironolactone is more effective,
but alone it is not a good general anti-androgen. However, in patients
for whom Spironolactone or Flutamide (discussed below) are problematic,
Finasteride is often prescribed as an anti-androgen that's better
than taking nothing at all.

There
is some argument over whether or not Natural Progesterone (also discussed
below) is more efficient tha Finasteride at blocking 5-alpha-reductase
activity. The dosages and methods seem to be a very important factor
in end result as one study found progestrone to be 97% efficient [
source
] at blocking 5-AR, while another found it only 24-62% effective [
source
]. The latter study found Finasteride to be 59-82% effective (a combination
of Pg and Finasteride was 68-78% effective) [ source
]. However, a different study showed Finasteride to be only 20% effective
[ source
]. So it remains unclear whether one is more effective than the other
or if they are roughly equal in effectiveness at blocking the enzymatic
conversion of testosterone to DHT. The only thing that IS clear, is
that Finasteride provides none of the other health benefits of natural
progesterone, which may be a major factor to consider when selecting
an HRT regimen. Note that these numbers refer to SERUM levels of 5-AR.
The enzyme is also produced at localized points in the skin, where
the efficiency of Finasteride is roughly cut in half!

Androcur/Cyprotone
Acetate: A popular anti-androgen outside the United States
is Cyprotone Acetate (it has not been approved by the FDA for use
in the USA). There is a commonly held belief among many transsexual
people that Cyprotone Acetate is the most powerful general antiandrogen
available. There are a number of pharmacalogical studies that have
shown Spironolactone to be the most powerful of the anti-androgens
available, especially when delivered transdermally. That being said,
there are many dermatologists who claim Cyprotone Acetate is more
effective, possibly because it is absorbed into adipose (i.e. "fat")
tissue nearer the skin and slowly released, while Spironolactone must
travel to hormone receptors in the skin via the bloodstream if taken
orally. Suffice it to say that one can potentially be more effective
than the other depending on what the application and desired chemical
action is. Spironolactone is available worldwide by prescription and
there is more data behind it's use, especially in TS HRT. Cyprotone
Acetate was developed to treat testicular cancers in men as part of
their chemotherapy. There have been no studies of the effects of long-term
use of Cyprotone Acetate that I could find.

If
you are switching to or from Spironolactone (Aldactone) and Cyprotone
Acetate (Androcur) be aware that Androcur is much more
powerful as an anti-androgen than Spiro, therfore you don't need
to take as much of it. The general rule of thumb for conversion
between the two is that Androcur is FOUR TIMES as strong as Spironolactone.
So, if you were taking 200mg/day of Spiro that would mean you'd
only need 50mg/day of Androcur. It is also suggested that you ramp
down off of or up onto Spiro over the course of two to three weeks
and start with no more than 25mg/day of Androcur until you are certain
you do not have any negative reactions to it. It is important to
have your liver function monitored while taking Androcur. Also be
aware that people who switch from Spiro to Androcur also often notice
a weight gain of between 5 and 20 pounds. Some of it is water weight
returning once the diuretic effects of Spiro dissipate.

Flutamide
vs. Spironolactone: It seems more and more Male-to-Female
TS patients are opting for (or are being placed on) a drug called
"Flutamide." This is a powerful, systemic anti-androgen
with a chemical action very similar to Cyprotone Acetate in that it
blocks the receptors for testosterone. Flutamide may be given together
with injections of another type of hormonal therapy drug (goserelin,
buserelin or leuprorelin). These drugs block the production of a hormone
produced by the pituitary gland (luteinising hormone) which normally
stimulates the production of testosterone. Flutamide should not be
taken as a monotherapy (i.e. by itself) by pre-op M2F transsexuals
because of the way it interferes with the normal negative feed-back
action of androgens, Flutamide stimulates gonadotropin production
and subsequently androgen production. Meaning, on it's own, it can
potentially INCREASE androgen levels! As for how Flutamide stacks
up against the other anti-androgens, in one study of women with hirsutism
(excessive facial/body hair growth) it was compared to Spironolactone:

Treatment
with the pure antiandrogen flutamide caused a rapid and significant
decrease (P < 0.05) in the hirsutism score, which became significant
after only 3 months of therapy. The maximal 50% inhibitory effect
(P < 0.01) was observed after 6 months of therapy, with a hirsutism
score similar to values found in normal premenopausal women. In
contrast, spironolactone caused an inhibition (P < 0.05) that
became significant after 5 months of therapy with an approximately
30% decrease in the hirsutism score (P < 0.01, flutamide versus
spironolactone). No further decrease in the hirsutism score was
observed up to the last time interval studied, namely, 9 months.
[ source
]

That being said,
For a small subgroup of women flutamide and other oral antiandrogens
are highly toxic. Between February 1989 and December 1994 the Food
and Drug Administration (FDA) received reports of 20 patients who
died and 26 who were hospitalized for hepatotoxicity due to flutamide,
a rate around 3 per 10,000 flutamide users. Early symptoms of hepatotoxicity
include nausea, vomiting, fatigue and jaundice and if such symptoms
occur they must be immediately reported to a doctor. Dermatologists
generally recommend that serial blood aminotransferase levels should
be monitored during the first few months of flutamide treatment. Any
adverse aminotransferase level changes suggest that hepatotoxicity
is a significant risk and flutamide use should be stopped. For this
and other reasons, some dermatologists do not use flutamide to treat
hirsutism however, the side effect risk of flutamide is no better
or worse than other oral antiandrogens

Studies that compare
flutamide to spironolactone or cyproterone acetate suggest that overall
the beneficial effects on reducing hirsutism are similar. Some suggest
flutamide is slightly superior and others say it is slightly less
superior. Initially flutamide was given to patients at high dose rates
of up to 250mg three times a day. However more recent studies indicate
that a similar improvement in hirsutism can be obtained with flutamide
doses as low as 62.5mg a day. The reduction in dose significantly
reduces the risk of side effects.

Flutamide
vs. Finasteride: Another study concerning male pattern balding
compared Finasteride and Flutamide. The effect on hair growth and
regrowth (on the head) showed Flutamide to be more effective at stimulting
the length of hair shafts. Both agents were similar in effectiveness
on diameter of the hair shafts. Also of interest to M2F transsexuals
would be the effectiveness of Flutamide on DHT inhibition as compared
to Finasteride. The following table shows the results of that study
on blood testosterone and DHT levels. The drugs were delivered transdermally
by a hydroalcaholic solution and a gel (the third item on the table
checked levels after administration of the carrier medium alone, without
any of the drugs).

Serum
T/DHT Levels (in nmole/L)

Group

T

DHT

Finasteride

7.2+6.9

0.91+0.57

Flutamide

5.8+3.1

1.06+1.62

Vehicle
(control)

8.9+7.4

1.10+1.02

Clearly
flutamide is more effective than finasteride at reducing serum testosterone
levels, but flutamide was similar to the non-medicated carrier medium
in reduction of serum DHT. [ source
]

CONSIDER
ADDING PROGESTERONE

Usually
TS HRT consists of just an estrogen and an anti-androgen. Most endocrinologists
consider progesterone "optional" but there are very good
reasons to consider it "essential." First and foremost progesterone
is the body's natural way to block an enzyme called 5-ARD (5-alpha-reductase)
which converts testosterone into DHT. Many TS patients choose to use
Finasteride (Propecia/Proscar) for this purpose, and it is quite good
at blocking the conversion, but Finasteride doesn't offer the other
benefits progesterone does. [more
on Pg benefits] [other
effects of progesterone] The bone-building enzymes called "Osteoblasts"
have a hormone receptor for progesterone. In post-menopausal women
on HRT who have been given estrogen it only helps combat loss of bone
density if their adrenal glands are still capable of producing high
levels of progesterone (a normal chemical response to high estrogen
is to produce more of the "balancing hormone" progesterone).
However, if the body isn't capable of countering the estrogen with
enough progesterone the person becomes "estrogen dominant"
and the estrogen may actually DECREASE bone density by acidifying
blood (which causes calcium to be pulled form bone stores to neutralize
it) and estrogen can also creat "microclots" in bones the
create weakening "voids." What the pharmaceutical industry
has been slow to admit is that doctors have been prescribing the WRONG
hormone to women for over half a century! Why? Because nobody owns
the patent on natural micronized progesterone. There's simply no profit
in it for them. Other natural progestrone benefits include lowering
"bad" cholesterol and countering rampant estrogen-driven
cellular division (particularly crucial if one has an estrogen-sensitive
tumor). Testosterone can also counter this cellular growth, by the
way. There is anecdotal evidence that progesterone is necessary for
rounder, fuller, breast growth as some of the tissues in the breast
are progesterone sensitive. Many TS women have reported additional
breast growth and "fullness" after taking progesterone -
even years after they had believed they had achieved all the growth
possible under estrogen-only HRT. [source
1] [source
2 summary page 1 / source
2 summary page 2 / full
book at Amazon]

Part
of the problem in verifying things where TS HRT is concerned is that
virtually no broad studies have been done. Almost all the data is
co-opted from studies done on post-menopausal women, which may very
well be an "apple to oranges" type comparison. The truth
is nobody knows if the data is transferable or not.

I
should also mention that, though the terms are used interchangeably
even by doctors, "progesterone" and "progestins"
are NOT the same thing! Many TS people take Medroxyprogesterone (Provera)
as part of their HRT, believing it will give them the same benefits
as micronized progesterone. Provera is NOT a substitute for Prometrium!

Prometrium
& Liver Toxicity: As
far as Prometrium goes, about 75% of what you ingest is broken down
in the liver before any ever hits the bloodstream. While this give
your liver some extra work, I haven't seen any studies indicating
progesterone or it's metabolites are particularly "liver toxic."
I'd be more inclined to say the polar opposite. One study I've read
found that progesterone increased the amount of a protein (called
Metallothionein or MT) that binds with heavy metals, thus improving
detoxification after exposure to things like Cadmium [ source
] That pretty well says to me that progesterone moving through the
liver actually INCREASES it's ability to detoxify, so I'm not going
to worry about whether the Pg is trucking through my liver or not!

SUMMARY:
The Ups and Downs of Progesterone

Studies:
The "Up" Side

General
Benefits
Mayo Clinic researchers surveyed 176 women taking natural micronized
progesterone who had previously taken synthetic progestins. After
one to six months, the women reported an overall 34% increase
in satisfaction on micronized progesterone compared to their previous
HRT, reporting these improvements: 50% in hot flashes, 42% in
depression, and 47% in anxiety.

Cardiovascular
Health
Studies at Wake Forest University School of Medicine have concluded
that synthetic medroxyprogesterone, in contrast to bio-identical
progesterone, increases the risk of coronary vasospasm. This narrowing
of major blood vessels surrounding the heart could potentially
lead to a heart attack. On the contrary, bio-identical progesterone
plus estradiol protected against vasospasm.

Skin
Health
Though progesterone does not increase skin thickness (1), it does
increase blood flow to the skin (2) resulting in an increased
ability to sweat and loose the extra heat through the skin (3).
Progesterone can also raise body temperature, enhancing the ability
to tolerate cold (4).

Bone
Densisty
Progesterone has stimulating effect on the bone building osteoblasts
resulting in increased bone building activity (4, 5, 6, 7, 8,
9, 10). This is due to a direct stimulation of the progesterone
receptors in osteoblast bone cells (11, 12), as well as an increased
secretion of IGF-1 and other growth factors by the bone cells
exposed to porgesterone (13, 14, 15). The most positive effect
is seen when estrogen & progesterone are used in combination
(16).

"Good"
Cholesterol
Natural micronized progesterone will not reduce the good HDL levels
that are enhanced by estrogen replacement (17), and will result
in higher HDL than when synthetic progestogens are used (18) .

This lipoprotein
(a) benefit of estrogen is not diminished by either synthetic
(medroxyprogesterone acetate) or natural micronized progesterone
(19, 20).

Epithelial
Breast Cancer
Cancers often develop in epithelial cells [which make up one of
the several tissues in breast composition].All cells have a finite
life span,and there is a balance between cell division and cell
death. When stimulated by estrogen,the BCL2 gene causes breast
cells to grow rapidly and prevents cell death.In ovarian carcinoma
cell lines and in breast epithelial cells, Progesterone induces
apoptosis [disintigration of the cell membrane] and upregulates
the P53 gene - a tumor suppressing gene (34,35). Tests have demonstrated
that “progesterone at a concentration similar to that seen
during the third trimester of pregnancy exhibited a strong antiproliferative
effect on at least two breast cancer cell lines (36,37).

It is also
noteworthy to mention how synthetic progestins such as medroxyprogesterone
acetate (Provera) or norethindrone occupy the progesterone receptor
site and inhibit the binding of endogenous progesterone to the
receptor. Synthetic progestins do not activate the P53 gene and
also prevents the production of the body's own progesterone (the
brain is tricked into thinking there is enough already). This
chemically induced progesterone deficiency, like natural progesterone
deficiency, may increase the risk of breast cancer because the
BCL2 gene is upregulated by estradiol and no corresponding downregulation
opposes that action.

General
Tumor Suppression
As mentioned above, progesterone can upregulate the P53 tumor
suppressing gene. This gene is present in tissue outside the breast
as well, so there can be a systemic suppression of cancerous cell
divisions.

Hair
Growth/Hair Loss
Finasteride (Propecia/Proscar) was found to be a major inhibitor
of dihydrotestosterone (DHT) formation. Even 1 nM finasteride
inhibited DHT synthesis in dermal papillae by 86% and 1 nM progesterone
by 75%. Estrogens were less able to inhibit the synthesis of DHT
in dermal papillae ( e.g. 100 nM 17alpha-E: 20%; 100 nM 17beta-E:
60%). Measurements were made on cultures done from scalp biopsies
with high-performance liquid chromatography analysis, which is
why test levels are reported in "nanometers." [ As reported
in the European Journal of Dermatology. Vol. 11, Issue 3, May
- June 2001: 195-8, Investigative Reports. "Influence of
estrogens on the androgen metabolism in different subunits of
human hair follicles" S. Niiyama, R. Happle, R. Hoffmann:
Department of Dermatology, Philipp University, Deutschhausstraße
9, D-35033 Marburg, Germany. full article text: www.john-libbey-eurotext.fr/articles/ejd/11/3/195-8/]

And to be
fair and impartial, I think I should say that there ARE some risks
or negative side effects that have ALSO been observed and studied
in relation to micronized progesterone:

Studies:
The "Down" Side

Sex
Drive
Excessive progesterone may decrease libido due to antiestrogen
and anti-androgen effect (21, 22). As well as decreasing libido,
excessive levels may induce depression (23).

Blood
Sugar
While estrogens help the cells of the body utilize glucose more
efficiently by making them more sensitive to insulin, progesterone
can cause a decrease in insulin sensitivity, having an effect
on blood sugar that is similar glucocorticosteroids 12. This interference
with the action of insulin can interfere with normal glucose uptake
and cause insulin resistance (24, 25, 26, 27, 28) .

The ability
of progesterone to interfere with proper function of insulin and
glucose has since been associated with gestational diabetes (29,
30, 31) as well as hormone replacement therapies (32,33, 34, 35)
and has been been observed in both synthetic & non-synthetic
progesterone (36, 37, 38, 39). Even the high progesterone levels
which occur naturally during the luteal phase can induce insulin
resistance in some women (21, 28) .

Progesterone-sensitive
Breast Cancer
Progesterone insufficiency may play a role in the development
of breast cancer (29), however progesterone may also play a role
in the proliferation of some progesterone receptor forms of breast
cancer - referred to as "PR+" breast cancer. There is
a test to determine whether breast cancer cells are estrogen or
progesterone sensitive. (30). This increased risk is associated
with the increased production of IGF-1 by breast cells stimulated
by excessive progesterone (31, 32) - resulting in the proliferation
of several forms of breast cancer cells (33).

Conclusion: Natural
progesterone (i.e. Prometrium) is the most effective at preventing
T-DHT conversion while medroxyprogesterone (i.e., Provera) is completely
ineffective. Even natural estrogen was more effective.

So, if the HRT
regimen is ethinyl estradiol and Provera the patient should supplement
with Finasteride (Propecia/Proscar) to inhibit T-DHT conversion. Obviously
taking Provera isn't going to inhibit the formation of DHT at all,
so there's no reason to take it.

I should note
that the above effectiveness percentages refer to SERUM levels. 5-AR
and DHT are also active at localized places within the skin, where
effectiveness is roughly halved. This makes a strong argument in favor
of using a topical form of progesterone if the purpose of taking Pg
is to combat the effects of DHT on hair follicles. As progesterone
tends to collect in fatty tissues any infused cream/lotion/gel/foam
should be applied at points on the body with high levels of blood
circulation and low levels of fat (a the wrists and hands for example).

Long-term use
of progestins like Provera have been more closely associated with
the development of breast cancer, while long-term use of progesterone
appears to offer a protective effect against breast cancer, possibly
due to an insulin-related effect that is present with natural progesterone,
but is not present when using progestins or just estrogen.

Q.
Will Provera or Prometrium increase breast size?

A.
Depends on what you mean by "increase." Among the side-effects
listed for both progestin and progesterone is "breast-enlargement."
This is a TEMPORARY condition that mimics the swelling of the breasts
when a woman is ovulating or when she is pregnant. Progesterone and
progestin cause fluid retention in tissues, which may be responsible
in part for the breast enlargement, but it is more likely due to a
downstream effect that increases the level of Prolactin. Once the
progesterone (or progestin) influence is removed the swelling effect
will reverse. HOWEVER, there is another factor to consider for someone
who is still developing breasts. Progesterone is the hormone that
promotes development of the lobules and alveoli in the breasts (i.e.,
the "glandular tissues"). It causes the alveolar cells to
proliferate, to enlarge, and to become secretory in nature. Estrogen
stimulates the non-glandular tissues (fatty tissues and fibrous tissue
called "Cooper's Ligaments"). [source].
Progestins, however, are sometimes prescribed to counteract precocious
breast development in adolescent girls (i.e., breast development that
is too soon or too much). Progestins are considered a successful therapy
for Benign Fibrocystic Breast Disease (FBD) to counter estrogenic
stimulation of Coopers Ligaments that can make breasts lumpy and dense.
Whether or not progestins stimulate the growth of glandular tissues
appears to be unknown. [source
1] [ source 2
] [source
3 ] [ source
4 ] [ source
5 ]

About
Progesterone Creams

Progesterone creams
purchased over the counter usually have very low amounts of the hormone
added. Anything less than 3% USP is considered "non prescription
strength" but also possibly ineffective as the primary ingredients
are basically lotion (skin moisturizers) that are not absorbed through
the skin into the bloodstream. The skin is a very effective barrier
to absorbtion, that's one of it's jobs. Prescription strength creams
are available using proven "carrier mediums" that CAN cross
the skin barrier into the bloodstream, but they are usually only available
as special orders through a "compounding pharmacy." I'm
unaware of any standard commercially available transdermal progesterone
product from a major pharmaceuticals company that could be purchased
at your local drug store. If you DO plan to try transdermal prescription
strength progesterone creams, effective amounts for F2M transsexauls
should contain 20-30mg of micronized progesterone per dose (this,
when absorbed into the skin, will yield roughly the same amount of
useful progesterone as a 200mg Prometrium pill.

Why use a transdermal
delivery? One is to prevent any chance of liver problems (though as
noted above, progesterone doesn't appear to be liver toxic itself).
The other is to focus 5-alpha-reductase blocking in the skin instead
of in blood serum. A certain amount of testosterone in the skin will
be convered to DHT at the skin level. That DHT is far more likely
to affect male pattern balding or unwanted facial and body hair growth.
I have seen references to alleged studies indicating that a blood
serum increase in progesterone is only 50% as effective at blocking
skin-level DHT formation as a prescription transdermal cream [ source
unknown, sorry ]. If this is true a M2F using progesterone to prevent
male pattern hair problems might find a topical delivery system yeilding
better results than either oral or injectibles (I'm not saying there's
any proof of that, however).

Oh, in Canada
they made sale of creams with ANY progesterone by precription only.
Also, see the end of this section for information indicating the OTC
creams sold in the United States may be in violation of Federal regulations
too.

About
Micronized Progesterone Injectables

Q.
What is the typical dosage for progsterone in oil IM injections? The
only dosage information I can find is on the Anne Lawrence/TS roadmap
sites. I [am] interested in frequency of injections as someone. .
. .insisted that pio IM injections would completely seep out into
the blood within a day and be largely broken down by the liver and
expelled by the body, and that I would have to take IM pio injections
on a daily bases.

A.
The short answer is there IS no "typical dosage"
for Progesterone in oil for IM injections. Here's why:

Dosages are different
depending on what is being treated and the amount of fatty tissue
the patient has.

Here's how it
works: the micronized Pg is suspended in oil. The oil is a "carrier
medium" that is readily absorbed - like a sponge - by fatty tissues.
This "stores" the Pg in the fat where it is slowly released
into the bloodstream over time (I've never seen figures for the absorbtion
rate nor the release rate). It is usually "cycled" with
doses off and on because you can reach a point of "super-saturation"
of fatty tissue with it and, like a waterlogged sponge, the tissue
simply cannot absorb anymore. So you have to have some "downtime"
that allows the Pg in fat stores to be released into the bloodstream
before you can administer more (think of it like letting the sponge
dry out a bit for a while before soaking it again).

Most Endos still
consider Pg completely unneccesary or optional for TS HRT - which
is something with which I seriously disagree, given what a potent
5-alpha-reductase blocker it is with additional health benefits for
bone building and cholesterol. Feminizing affects are minimal, and
that's based largely on anecdotal evidence because no studies have
been done with TS women. Though in natal females it is known to stimulate
the growth of one of the the three kinds of breast tissue that firms
and rounds the breast structure, so I'd say any Endo that didn't include
Pg wasn't doing everything they could for the patient's breast development.

Anne Lawrence's
suggestion sounds like a "minimum starting dose" to me.
Based on what I've read of Pg supplementation, a woman sees best benefit
from a "maintenance dose" of about 20 mg/day into the bloodstream.
For other methods of delivery this would require dosing much higher
to compensate for the loss of some Pg to destruction and enzymatic
conversion to other substances (about 90% for oral, 20 - 30% for transdermal
or sublingual). Injections, though, generally are close to 100% efficient
in delivering Pg into the bloodstream. If 50mg was injected in, say,
saline it would all move right into the bloodstream. In oil, however,
most of it is carried into fatty tissues and only a portion of it
is released into the bloodstream each day thereafter. As I said, I've
never seen figures for the release rate.

I've also read
that you probably wouldn't want to take the 100mg injections because
they reportedly cause "excessive burning and aching" at
the injection site - so much so I found doctors on one Endocrinology
message board advising 100mg Pg in oil be injected with Lidocaine
to mitigate the pain!

The only real
way to know how much to use would be to get a baseline Pg test done,
then do a minimal injection regimen, have the level re-tested and
see how much it boosted the serum level and adjust the injection amount
and/or frequency up or down until it's close to the "target level."

Ideally for a
TS woman (and this is just my non-doctorly opinion) the target level
should be above that of a post-menopausal woman (which would be the
same as for a male), but below the range for a woman's luteal phase
of her cycle (so kind of in the upper portion of follicular or inbetween
follicular and luteal). For example, the generic reference range I
have indicates that the range would be between 1 - 4 ng/ml, so a good
"target" would be about 2 - 2.5 ng/ml. But labs use their
own reference ranges to compensate for the methods and calibration
of their equipment, so it's important to use THEIR numbers.

Even though the
manufacuterer of Pg in oil for IM injections say the max daily dosage
is 200mg, there are a couple of reasons that a TS woman wouldn't want
to mega-dose on progesterone:

1) In a natal
female the level of Pg goes up during ovulation and skyrockets during
pregnancy. If a non-pregnant person (physiologically male or female)
takes huge amounts of progesterone it "tricks" the brain
into thinking that the person is pregnant and starts "priming
the body" for gestating a fetus and milk production. This is
called a "Prolactin Response" because the person's body
starts producing prolactin hormones (the ones that cause lactation).
If a person is cycling with large amounts of Pg, repeated "Prolactin
Responses" can lead to the formation of a "Prolactinoma"
in the brain, which is a benign, non-cancerous enlargement of the
anterior pituitary gland that can disrupt other hormone levels in
the body.

2) The body generally
tries to make good use of what hormones are available. In the case
of Pg it stores excess in fatty tissues or enzymatically converts
Pg into other hormones. Leftovers are either broken down by the liver
and expelled from the body (usually in urine) or some of it just oozes
out of the body in other fluids (like saliva). If you have HUGE amounts
of Pg in your system and there isn't any more room in fat to store
it (because it's already saturated from supplements), you can over-tax
your liver and waste a bunch of it as it is broken down or otherwise
simply expelled from the body, but more importantly, your body will
likely first try to enzymatically convert it to testosterone. This
is likely the underlying cause of the "virilazation" (mostly
unwanted facial or body hair growth) reported by some men and women
who've taken Progesterone supplements - and what likely has also led
to the general belief that it is undesirable as part of TS HRT.

In lower doses,
though, this enzymatic conversion is less of a problem and can be
further mitigated by combining Pg supplements with Spironolactone,
which happens to suppress expression of the P-405 gene responsible
for signalling enzymatic conversion of progesterone into testosterone.

Because Pg in
oil that is injected is moved into fatty tissue, the dosage is often
also adjusted based on the amount of fat the person has. A skinny
person without much fat would have less tissue to absorb the oil -
if you gave them the same dose as a fatter person a larger portion
of the injection would be swept into the bloodstream directly, rather
than absorbed.

Frankly, transdermal
or oral are a little easier to figure out how much you'll be getting
into the bloodstream - even though some of it is destroyed in the
process of getting there. The other advantages to transdermal or oral
administration are that you don't have to cycle on and off (which
can create PMS-like symptoms, as it essentially mimics the fluctuations
of a woman's menses - there is no medical advantage for a TS woman
- or a post-menopausal woman for that matter - to duplicate the menstral
cycle). Other methods of delivery may be a bit more "wasteful,"
but they provide means for a persistent, stable level while injections
(by their nature) cause an initial "surge" in levels that
tapers off over time until another injection creates another surge,
and so on and so on.

So the answer
is - there ISN'T a "typical dosage" and blood tests for
Pg will have to be done and various regimens tried until serum levels
are close to the target level. That's the nature of Endocrinology,
though. It's an inexact science requiring repeated testing, monitoring,
and adjusting to "tailor" the drugs to the unique chemistry
of the individual patient. "Typical dosages" for any HRT
drugs are merely "suggestions" within a "safety zone"
of minimal and maximum amounts.

Probably not the
answer you want to hear, but that's why you probably can't find a
solid number. There isn't one.

That person who
told you intramuscular injections would seep out in a day is wrong.
These injectibles are specifically designed (by suspension in oil
to carry it into fat stores or by the addition of an ester) to remain
in your body for extended periods of time and gradually become bio-active
over the course of a few days (you may find you'll need to juice yourself
with the estrogen more often than the progesterone, since it appears
it metabolizes and expells from your system faster than the progesterone
will).

PROGESTERONE
COUNTERPOINT:

In the interest
of remaining objective and giving time to both sides of an issue,
I am obligated to inform you that much of what the creams promise
is based on the work of the late Dr. John Lee, who was widely
regarded as an authority on the subject of progesterone supplements.
However, if you look at this
collection of information (much of it referenced to the OB/GYN.net
message board) you'll see that he's pretty well considered in
some circles to have been a quack with allegations that his "research"
findings can't be reproduced in a strictly controlled study. Almost
every web site I've seen selling a progesterone cream refers to
Dr. Lee's work. The only thing that's obvious is that many claims
about progesterone (specifically in relation to OTC creams) are
hotly contested. Furthermore that it appears that the OTC creams
may actually be illegal in the United States too, according to
FDA guidelines (though they don't seem to be cracking down on
it because the evidence sorta indicates that the creams aren't
actually HURTING anyone).

Because there
is some question concerning verifiable benefits of progesterone
supplementation I have chosen to focus primarily on known biochemical
reactions such as 5-alpha-reductase blocking, osteoblast enzyme
stimulation, and P-53 gene down regulation rather than on vague
and largely anecdotal "evidence" regarding how it made
someone feel. I should point out that biochemical reactions observed
in a lab may not translate directly to biochemical reactions in
the human body in terms of end effect. For example, if a reaction
is seen to affect 90% of a sample in the lab that doesn't necessarily
mean the same effectiveness will be seen in the human body where
there will be other variables that may decrease the efficiency
of the chemical reaction.

HELP!
I'M LEAKING!

Occasionally
M2Fs taking hormones will experience fluid (usually kind of yellowish
in color) leaking from their nipples. This usually occurs subsequent
to an orchiectomy or SRS where the person hasn't changed their pre-operative
dosages, or if they suddenly lower their dosages dramatically (specifically
dropping progesterone and/or estrogen). Don't freak, the leak is normal!

What has happened is the person inadvertantly tricked their brain into
thinking a couple of things about their body that aren't true.

Natural
Male Lactation

"In
1992 eighteen Dayak fruit bats [Dyacopterus spadiceus]
were captured from a rainforest in the Krau Game Reserve, Pahang,
Malaysia. Of the 10 mature males captured, each had functional
mammary glands from which small amounts of milk were expressed.
It is not known whether the males actually feed young. The reason
this could happen is that a breast is a breast is a breast. Male
lactation is physiologically possible and has been observed in
some domesticated mammals and even humans. Dr. Robert Greenblatt
says that milk production in human males can be stimulated by
letting a baby suckle for several weeks. Indeed some males, either
at birth or puberty, secrete milk. Historically male lactation
has been noted by the explorer Humbolt, who spoke of a 32 year
old man who brestfed his child for five months. It was even observed
in a 55 year old Baltimore [Maryland] man who had been the wetnurse
of all the children of his mistress!"

-
Professor Patty Stuart-Macadam of the Department of Anthropology
at the University of Toronto.

First,
when they have had an orchiectomy their estrogen and progesterone levels
were no longer "opposed" by testosterone or any amounts of
the "downstream" androgens that were competing with for hormone
receptors. The result was the same as if the person had suddenly, and
dramatically, increased estrogen and progesterone intake.

This tricks the brain into thinking the body was pregnant. Expecially
the progesterone, in biological females the levels go through the roof
during pregnancy. It doesn't matter whether you're born male, female,
or intersexed, the wiring for all this is "primitive" and
not gender-specific. It's why males still have nipples, even though
they generally don't serve any purpose - except possibly in at least
one species of Malaysian bat, where the males may nurse the young [see
sidebar].

During a woman's pregnancy, the high level of progesterone triggers
an increase in the amount of another hormone called prolactin. There
are hormone receptors on the milk glands in the breasts that react to
prolactin, which stimulates them to start producing milk.

The
first thing a M2F will probably notice (and may actually, initially,
be quite pleased with) is a swelling in size of their breasts as they
become laden with fluid from Stage One Lactogenesis. Even if there are
high levels of prolactin, the "release" of the milk is inhibited
by the presence of high levels of progesterone. The Stage One Lactogenesis
can be triggered either by suddenly, and dramatically increasing estrogen
and/or progesterone intake, or by maintaining pre-operative dosages
post-operatively (i.e., post-SRS or post-ocrhicectomy).

When a M2F person then cuts their dosages, specifically the progesterone,
they inadvertantly mimiced the sudden drop in progesterone that happens
when a woman gives birth. That triggers Stage Two Lactogenesis (also
called "copious milk production"). This typically begins 30-40
hours after the drop in progesterone, but actual lactation usually doesn't
start for 50-73 hours (2-3 days) after birth, so the M2F experiencing
breast leakage most likely won't notice it until more than two days
later, and may not make the connection that cutting their dosage triggered
the lactation. As mentioned at the beginning of this section, the fluid
is often yellowish. This is because it's what is called "foremilk"
which is very high in fat content, and fat is yellow in color.

After that first few days, the endocrine system no longer controls the
lactation. It enters what is called Stage Three Lactogenesis (Autocrine,
or Local, milk production). Removal of the milk and stimulation of the
nipple (i.e., as in via nursing a baby) triggers additional releases
of prolactin that perpetuate milk production. If you don't remove the
milk/fluid your body will absorb it and the prolactin levels will drop
and your endocrine system will stabalize. The breasts will begin
to shut down milk production within several days if milk is not regularly
and effectively removed (like by a nursing baby).

Since the body has been tricked into thinking it has given birth, it
is also possible that the sudden drop in hormone levels could mimic
post-partum depression, another side-effect M2Fs often suffer generally
that might worsen so they may not immediately associate it with their
hormone therapy.

One last thing to consider if you are lactating is that lovemaking (sexual
stimulation) releases a hormone called oxytocin, which has been associated
in both biological females and M2F transsexuals with an ejection of
liquid from the nipples (either a spray or a flow, depends on the person).
You may want to issue your partner a set of swim goggles! Seriously,
though, stimulation of the breasts during sex could actually prolong
the lactation (see Stage Three Lactogenesis above).

THE
TRUTH ABOUT PROLACTIN

I've
heard a number of M2F TS people discussing the "benefits"
of increasing their prolactin levels or how lactation (or leakage) from
their nipples is a "good sign." I'm afraid I'd have to beg
to differ. Increased levels of prolactin in anyone other than a nursing
mother are not a good sign at all!

First
of all, if you aren't taking any hormone medications and are experiencing
lactation get yourself to a doctor post haste! It's a symptom of a pituitary
tumor or prolactinoma in your brain.

If
you're taking progesterone supplements see the information above about
how that could potentially stimulate a release of prolactin as well
as potentially cause the formation of a prolactinoma. Yes, in your brain.
Generally I don't like any sentence to end with ". . .in your brain."
You shouldn't either.

One
drug some M2F TSs take trying intentionally to stimulate prolactin,
under the belief that it will stimulate breast growth, is Domperidone.
No, it isn't wine. That's Dom Perignon.The drug (not the wine) is also called
Motillum and Evoxin. One
place people seem to have gotten the idea of using this was from Annie
Richard's "Birth of Venus" web site (and to be fair, other
places online where TS HRT info is shared). Annie's site is wonderful,
but I have to take issue with the following statements from her web
site:

"...transsexual
women gain considerable benefits from the breast developing effects
of prolactin even if its not initiating lactation because of their
high oestrogen intake, and thus should not be deterred from early
use. . . .Generally, start at 20 milligrams (two 10 mg tablets) four
times a day, i.e. about every 6 hours. After starting domperidone,
it may take three or four days before any effect is noticed, though
sometimes women notice an effect within 24 hours. It appears to take
two to three weeks to get a maximum effect. Most women take the domperidone
for 3 to 8 weeks."

I find the claims
dubious at best. Prolactin has no breast developing effects. The key
word there is "developing."

Progesterone is
the hormone that promotes development of the lobules and alveoli in
the breasts (i.e., the "glandular tissues"). It causes the
alveolar cells to proliferate, to enlarge, and to become secretory in
nature. Estrogen stimulates the non-glandular tissues (fatty tissues
and fibrous tissue called "Cooper's Ligaments"). [source].

The aforementioned
hormonal actions on breast tissue development are why I maintain that
you cannot achieve "female breasts" on estrogen alone! Estrogen-only
HRT will cause a "side-effect" increase in progesterone up
to a point, which will stimulate *some* glandular tissue growth, but
female bodies produce progesterone in the adrenaline glands AND the
ovaries. M2F TS's can only produce it in the adrenaline glands. Since
we're pushing for pubescent girl levels of hormones to stimulate initial
breast development I don't think it's physically possible, without progesterone
supplementation, for a M2F TS to get the full, firm breast development
biological females have [source].

All Prolactin does
is stimulate those alveoli to swell and secrete milk. If you don't have
all that much prolactin stimulation OR if you don't have that many alveoli
(as M2F TSs often don't) it is unlikely that what they secrete will
ever build up in sufficient quantitites to come out of the nipples in
the same way as a nursing mother - a fluid swelling of the breasts may
be all that happens or a small amount of clear (or nearly clear) liquid
may leak from the nipples. Progesterone also causes some fluid retention
in breast tissues so if no liquid is being secreted from the nipples
it would be hard to say whether the fluid swelling was due to prolactin
or progesterone (especially if you're also taking progesterone supplements).

I should also note
that Domperidone (Motillum, Evoxin), while often prescribed for increasing
breast milk production in nursing mothers, was not developed for that
purpose. It is a drug for treating gastrointestinal disorders like gastroenteritis.
[source]
It's actually a dopamine-receptor blocking agent that has as a side-effect
stimulating the Pituitary Gland to produce prolactin. In general the
drug is considered quite safe, even for use over a course of several
months.[source]
However, incidence of gynecomastia and lactation have been reported
in biological males taking the drug - though it is listed as a "less
common" or "rarely occurring" side-effect.[source
1] [source
2] This suggests to me that the increased prolactin levels may be
effecting OTHER hormones, primarily progesterone, that in turn causes
growth of glandular breast tissue. People tend to forget that these
hormones are all inter-linked with feedback loops and enzymes that convert
them to other things.

What this means
for a M2F TS is anybody's guess. Here's my guess:

I suppose it's possible
it could stimulate an increase in breast-building hormones (those would
be estrogen and progesterone), though I think it would be FAR more effective
to just take extra estrogen and progesterone if that's what you're really
shooting for. More than likely it is simply causing whatever alveoli
you've got to start cranking out fluid, which will probably be contained
in your breast tissues because you won't produce "nursing level"
amounts of it, and the fluid swelling (i.e., the increase in breast
size) will probably go away shortly after you stop taking Domperidone
just as it does for nursing mothers taking it.

So, in short, I'm
not denying it could probably swell your breasts, but I'm inclined to
believe that swelling will reverse as soon as you stop taking the drug
just as they do for those nursing mothers taking it.

Q: If
it's actions are temporary in biological females, why would they be
permenant in transwomen?

Estradiol
Valerate
- I looked up what the difference is between it and Estradiol. Regular
Estradiol is listed as "17-beta-Estradiol" while Estradiol
Valerate is called "Ester of 17-beta-Estradiol." This made
me wonder what the heck an "ester" was. I learned it is
a molocule attached onto the steroid backbone that prevents it from
latching onto hormone receptor points immediately, especially right
around the injection site. The body has to first break off the "ester"
that was added before the hormone can become "fully functional"
and bind with estrogen receptors. Different esters take different
amounts of time to be broken off the steroid backbone, which determines
how long the injection remains "active" in your system.
According to Schering Pharmaceuticals the Pharmokinetics of Estradiol
Valerate are:

"Estradiol
valerate is rapidly and completely absorbed. The steroid ester is
cleaved into estradiol and valeric acid during absorption and the
first liver passage. At the same time, estradiol undergoes extensive
further metabolism, e.g. into estrone, estriol and estrone sulphate.

Maximum
concentrations of estradiol in plasma are generally reached between
4-6 hours after tablet intake. In relation to the single dose, approximately
two times higher serum levels of estradiol are observed after multiple
administration. On average, the concentration of estradiol varies
between 30 (minimum levels) and 60 pg/mL (maximum levels). Estrone,
as a further estrogenic metabolite, reaches about 8-times higher
concentrations in plasma. After stopping the treatment, pre-treatment
levels of estradiol and estrone are reached within 2-3 days.

Estradiol
binds to albumin and the sex hormone binding globulin (SHBG). The
unbound proportion of estradiol in plasma is about 1-1.5 % and the
SHBG-bound proportion is in the range of 30-40 %.

After the
ester cleavage of the exogenously administered estradiol valerate,
the metabolism of the drug follows the biotransformation pathways
of endogenous estradiol. The metabolic clearance of estradiol has
been found to be about 30 mL/min/kg. The metabolites of estradiol
are excreted with a half-life of about 1 day; by about 90 % via
the kidneys and by about 10 % with the bile."

Understanding
"Synthetic" Estrogens

One thing that
confused the heck out of me at first was how the pharmaceutical industry
uses the word "synthetic" in regard to hormones like estrogen.
It has nothing to do with the original SOURCE of the drug, nor does
it have anything to do with the process. The terms refer exclusively
to whether or not the end product is chemically different from what
the human body produces.

For example, Premarin
- though it comes from a natural source (pregnant mare urine) - is
biochemically different from what the human body produces (because
it is horse estrogen). Technically it is a "synthetic."
However, Wyeth-Ayerst Laboratories decided to market Premarin as "natural"
because of the animal source, rather than on its biochemical nature.
When they aren't selling a bill of "natural" goods Premarin
is simply called "conjugated estrogen" because it is a mixture
of TEN different estrogens - including equilin and equilenin;
both of which the human body has no enzymes to metabolize (because
those are the horse estrogens). The main "human estrogen"
in it is the weaker estrogen called Estrone (E1), which is normally
the metabolized result of Estradiol (E2), though there is reportedly
a little bit of Estradiol in Premarin as well. You may question why
I called Estrone "weak." Many sources online claim it is
the "most powerful estrogen," which isn't true. It may be
the most DANGEROUS of the estrogens, however, because of its association
with stimulating cancer cells in the breast. I don't know where those
other folks got their info, but the medical resources I've consulted
say Estradiol is the Queen of estrogens and Estrone and Estriol it's
underlings.

The estrogen in
most of the drugs that contain 17-beta-Estradiol is synthesized in
a lab from plant extracts. Okay, so it's made in a lab but it comes
from a natural source too. "Natural" or "Synthetic?"
In this case "Natural" because the resultant molocule is
bio-identical to that produced in the human body.

As for Ethinyl
Estradiol (also called Estinyl Estradiol), it is a synthetic designed
to be more powerful than endogenous estrogen with a very long half-life
in the body (designed to make it very difficult for the liver to break
it down). Incidence of thrombosis are primarily linked to this estrogen.
Some women have suffered thrombosis on just 0.035mg/day, but some
M2F transsexuals have survived up to 1mg/day. The danger is real enough
that the .50mg pills are no longer even manufactured! I personally
think the manufacturer's choice to market it under the name "Estinyl"
was to purposely create confusion with Esterafied Estrogens, or those
created with an ester of 17-beta-estradiol (i.e., Estradiol Cypionate,
or Estradiol Valerate). All of which are not nearly as dangerous as
Estinyl/Ethinyl Estradiol.

THE
GREAT SYNTHETIC UNKNOWN:

There
is this class of compounds called "selective estrogen receptor
modulators" (SERM). SERMs act like estrogen in the central
nervous tissue, but not in other tissues susceptible to cancer-causing
effects of esterogens. Well known SERMs would include Tamoxifen
and Raloxifene. Both drugs are used in the treatment of female
osteoporosis and breast cancer. A new compound, called STX has
also been discovered to have SERM activity [ source
]

So what
does this possibly mean for M2F transsexuals? Well, for those
who are in the process of feminizing their bodies probably nothing.
For those that have seen their maximum feminine development,
are post-op, and are concerned about developing breast cancer
from continued, long-term estrogen supplements - but who do
not want to give up the psychological benefits of estrogens,
SERMs may provide an alternative long-term option for their
HRT.

If you look
under the drugs listed for F2M transsexuals you may notice that
Tamoxifen is listed there as an estrogen BLOCKER, so you may
be wondering why on Earth a M2F transsexual would ever consider
taking it? SERMs are considered estrogen blockers because they
occupy the hormone receptors in tissues but do not stimulate
the cells in the same biochemical way. They DO, as mentioned
above, act like estrogen in central nervous tissues - which
are the tissues that benefit from the psychological effects
of estrogens (which addresses things like memory loss and depression).

I frankly
have never heard of a M2F transsexual using Tamoxifen or Raloxifene
as part of her HRT regimen. Most likely because it seems counter-intuitive,
given the drugs' reputation as a estrogen blockers. However,
a closer look at the biochemistry involved shows that drugs
like Tamoxifen still function as estrogen in select tissues
but not in others. Once a M2F person has seen their maximum
breast development estrogen supplements pose a cancer risk,
especially since the drug will usually be taken for the rest
of the individual's life. An alternative that still provides
the psychological benefits of esterogen without presenting the
cancer risk is a possibility that should not be overlooked by
transwomen who are years past their final feminization results
and post-operative (therefore not at risk of becoming androgen-dominant
again, which could potentially reverse some of the feminization).
Though optimal risk vs. benefit results would probably be achieved
through a combination of Tamoxifen with estrogen, the exact
amounts of each to assure the Tamoxifen didn't cancel out the
estrogen is probably best left to a qualified Endocrinologist
armed with more knowledge and lab results.

Any takers?

ESTRADIOL:
THE "SUBLINGUAL SOLUTION?"

One
reason many people don't like to take oral Estradiol formalations is
because of the extra load they put on your liver. As mentioned previously,
the amounts of estrogen in pills is actually quite high because a significant
amount of the active hormones (~90%) will be destroyed in the process
of digestion and the first pass through the liver before the drug ever
reaches your bloodstream. Subsequently whatever your body couldn't use
passes through the liver again to be broken down and excreted. The liver
was only designed by nature to clean out small amounts of "leftover"
hormones. The pills, though, overwhelm the liver's capacity to deal
with the amount, thus allowing some of the active hormones to escape
destruction in the liver and move into the bloodstream. Meanwhile you're
poor liver is working overtime, not to mention dealing with a hormone
that is, itself, "liver toxic" and damaging to liver tissues.
Okay, so what are you to do?

The
most popular solution in the Transgender Community is to dissolve the
estradiol pills either under the tongue (sublingually) or between the
cheek and gum (usually while sleeping). The inside of the mouth is loaded
with "mucous membranes" through which the hormone can easily
pass into the bloodstream without first passing through the liver. Not
only is there that benefit but there is also a great potential for higher
yield from each pill because sublingual absorbtion is much more efficient
than swallowing the pills. Instead of destroying ~90% of the hormones
in the pill, only ~20-30% may be destroyed, which can significantly
increase serum estradiol levels and better stimulate the process of
feminization.

It
should be noted that, while many TS people take estradiol this way,
this method of taking the drugs has never been studied to measure the
actual effectiveness and it is not the recommended method of administration
by the drug's manufacturer so if you do this, you do this at your own
risk! Also be aware that some drugs are "coated" to prevent
them so easily being destroyed by the stomach acids or to slow the dissolve
time for "time release" action. For example the animal-friendly
alternative to Permarin, the conjugated estrogen "Cenestin,"
has a "time release coating" that would make it less viable
(perhaps completely unviable) for sublingual dissoving.

HRT
Regimens by Dr. Thomas Waddell (PDF file on this site)Note: M2F specific information is on pages 6 - 10
I would also ignore their information under "Progesterone"
as they are only referring to Medroxyprogesterone, not the real stuff.